Lecture #2 | Terminology and Epidemiology of Cancer

Carcinogen

Anything that causes cancer

• things in the environment that act on DNA, RNA, or proteins

• Also hereditary causes to cancer

Epidemiology

Provides clues about heritable and non heritable causes of cancer through the study of incidence, distribution and determinants of disease in human population

Concept: Tumors are clonal

Tumors arise from one ore more cells that grow uncontrollably, creating a clone

• while all cancer cells are derived from one cell, they are all not the same due to a mixture of cell types

  • Tumors are heterogenous

  • This causes difficulties in controlling it

How do tumors come about

From a series of events affecting one cell

• cell with mutation clones itself

• cells with mutations are more likely to develop further mutations

• will continue to clone cell with larger and larger amount of mutation

Concept: Tumors arise from a series of events

1. Initiator

2. Promoter events

Initiating event

Creation of a mutation in a cell

• mutagens

  • 90% of all mutagens are carcinogen

  • not all though as some mutations are beneficial

  • a single event can be sufficient to cause a mutant

• inherited mutations

Promoter event

Compounds applied to an organism previously treated with an initiator that cause cancer, promotes cell proliferation

• not direct mutagen but may cause mutations indirectly

• induce cells to proliferate (replicate DNA)

  • anything that encourages cells to grow: hormones, phorbol ester (TPA), saccharin (rodents)

Promoter

Compound that induces “initiated” cells (mutants) to replicate in an un restricted fashion

• so almost anything that causes cells to replicate can be a promoter

  

• come in all shapes and sizes, many are man made, others are naturally occurring

Complete carcinogen

Acts as both initiator and promoter

ex: cigarette smoke contains >1000 chemicals

Concept 3: Timing and repetition of promoters are important

Promoters follow initiators

Promoters must reach a certain threshold

Scenario 2: While time elapsed, an initiator event is permanents

Scenario 4: Promoters must reach a certain threshold

Scenario 5: A lot of mutations means that there is no promoter is needed

Phorobol ester (TPA)

Dioxin (TCCD)

Estradiol benzoate

Concept #4: Progression follows initiation and promotion of the tumor

Progression can reduce the time that a mutation can take to proliferate

• from 10-20 years with initiation + promotion to months-years with just progression

Why does it take years to form a tumor?

Because their are checkpoints in cell growth

Concept #5: There is a delayed onset from the initial exposure to a carcinogen and when the cancer/tumor is first observed

Concept #6: Cancer is a multistep process that arises from multiple initiating and promoting events

Require steps (grouped into 6 categories) for cancer cells to undergo all the necessary changes to be fully malignant

• each step takes time

  

all steps need to keep happening

Concept #7: Classification of tumors depends on the stage of the tumor and its tissue of origin

if promotion is removed in early adenoma, it can regress

Benign (adenoma)

• Differentiated

• Normal structure, look like surrounding cells

• Slow, progressive growth, few mitoses

• Encapsulated

• Not metastatic (not traveling)

• Seldom harm to the host

well formed

Malignant (carcinoma)

Will keep growing

• Dedifferentiated

• Atypical structure, embryonic-like

• Rapid growth, very mitotic (identify spindle formation and condensation of chromatin)

• Not encapsulated

• Metastatic (invades other tissue)

• Significant harm to the host, due to metastases